Over 2 million workers in the US are exposed to laboratory animals in the course of their jobs, including research scientists, research technicians, and animal handlers. From 20 to 50 percent of them complain of symptoms related to animal exposure, and up to 1/3 of symptomatic workers are temporarily restricted or permanently removed from their jobs. However, not all symptoms are due to allergy; only 38 to 67 percent of symptomatic workers are sensitized (by prick skin or RAST tests) to the animals with which they work. This proposal addresses the discrepancy between symptoms and true allergy. Laboratory animal workers are exposed to animal allergens, particulates, and endotoxin in their job. Airborne endotoxin is a leading candidate exposure that may trigger symptoms in the non-allergic workers. To test this hypothesis, I will conduct an epidemiological survey of laboratory animal workers at NJRMC using questionnaire and prick skin or RAST tests to characterize symptoms, and aeroallergen and lab animal sensitization. Air sampling will measure endotoxin, real-time particulates, and mouse allergen in the animal care facility and in representative mouse research and unexposed laboratories. Univariate analysis and polychotomous logistic regression will measure the relationship between exposures, symptoms and specific sensitization. The results will describe the odds ratios associated with each exposure for the development of symptoms, sensitization, or both. Nasal IL-1beta and TNF-alpha are response cytokines typical for both endotoxin exposure and allergic rhinitis that will be evaluated in a case-control study nested within this cohort. Nonatopic nonsensitized, and atopic lab animal sensitized workers will be challenged with nasal endotoxin, allergen, and both, and early and late response symptoms, IL-1beta and TNF-alpha measured in the nasal secretions. These studies will provide insights into the role of endotoxin, allergen, and particulates in triggering symptoms, nasal cytokines, and specific allergy to laboratory animals.